Decoding the Genetics of Infertility

On our quest to answer questions about genetics that aren’t being asked as often as they should be, we found ourselves in the presence of an expert on the subject (in this case, Infertility). Dr. Priya Kannan, a prominent Embryologist and Consultant in Reproductive health and Human genetics. Though she was busy, she found time to satiate our curiosity and to spread awareness about infertility and its genetic basis.

Dr. Priya Kannan talks about Infertility and its scenario in India

Our first question was why we kept hearing about infertility so often recently. Because, when we were kids, we didn’t even know there was something like that. But nowadays, even 10 year olds are accustomed to that word. This is what piqued our interest in the first place. Her response was an eye-opener.

Statistically, infertility occurs in 1 in 8 couples and in married couples. 15% of all married couples are expected to not be able to get a child by natural means. After marriage, especially in India, there is a social pressure on the couple to be “blessed” with a child or two in the following year.

This has led to more people realising that something might be off. 50 years ago, even with an abundance of infertility clinics, no male would have come in for a check-up. He would’ve just gotten a second marriage and gone on with his life. Even if he did, they were too shy to give any samples. But nowadays, people are more open and forthcoming. Also, there has been a huge boost in the technologies and resources that we have now. In Chennai alone, we have about 45 well equipped IVF centers and there are more than 2000 centers in India, which is more than any other country. For a country with population crisis, we sure have a lot of IVF centers. There has also been a lot of improvement in the diagnosis and treatment technologies since the 80’s. In the beginning, the success rate was 10 – 15%. Now, it’s close to 40 – 50%. In case of surrogacy, it’s about 60%. There has been more awareness about this problem and more people are coming up for diagnosis and treatment. Before, people come and say that they’ve been married for 10 years and didn’t have any kids. But now, some people come after two or three years and some come after about one month and say that they think they might be infertile. The publicity is good in one way, but there are some flipsides. It goes both ways.

We were really surprised that advancements in air purification and cryopreservation could factor in so much in helping someone bring a life into this world. This is one of the many ways by which advancements in science as a whole could positively affect each and every small niche in the spectrum. Our next question was a bit obvious as we were students of genetic engineering.

How much of a role does genetics play in infertility?

Genetics has a very mysterious place in the diagnosis of infertility, because genetic testing isn’t done unless the male has a sperm count of less than 5 million. This is a definite indication that there is at least a 25% chance of a chromosomal anomaly. Chromosomal analysis is a must in such situations. Also, because there are variations which are otherwise completely normal, but have implications in the reproductive area. If the count is abysmally low, we have to do a Y chromosome microdeletion analysis, which will tell us if sperm can be taken from the male. In case of secondary infertility, which means that the mother gets pregnant but is not able to carry through with the pregnancy, both the partners’ chromosomes are analysed. But that is as far as genetic testing for infertility goes. There are some new opportunities though, like DNA fragmentation in sperm cells. It’s not an absolute indication for infertility, but it’s a new frontier that we’re exploring now.

IVF development of an embryo

Having said this, I still think that genetics plays a more prominent role that we give credit. I have personally seen many perfectly formed egg cells that failed to implant multiple times and when they opt for a donor egg, which was comparatively shabby, it gets implanted in one go. I have seen donor eggs getting implanted in the first try in the same uterus that rejected eggs from the same woman. There is something at the molecular level that makes certain people for fertile and potent than others.

On the other hand, PGS (Pre-implantation Genetic Screening) was discarded because of technological barriers and they weren’t giving any increase in success rates. But with the advancements in sequencing, I can get all 23 chromosomes screened and it’s coming out in a big way. PGD (Pre-implantation Genetic Diagnosis) is a boon for parents with a problem in their families. It’s absolutely amazing.

These are all the genetic testing that we’re practicing right now. I believe that there is something at the molecular level which influences the fertility of a person. I don’t know what Nobody has done any study on it, but it is my gut feeling. Everything will be explained by genetics at some point of time.

What are the diagnostic methods that you use for detecting infertility?

Well, for infertility, we look at the three major things: The sperm, the egg and the uterus. In some cases, the fallopian tube also has to be looked at.

For sperm, a semen analysis can tell us whether the male is able to give out a semen sample, if he is able to give it at will, the sperm count (or absence) and how much of it are motile. We’ll get all four of these in one simple test. Also, the sperms can be fixed for morphology studies. This is actually interesting because as per Kruger strict criteria, at least 4% of the sperm should be normal looking.

For the female, we cannot see the egg in any scan, but we can scan for the follicle, which houses the egg.

The uterus is still an enigma. Only the thickness and vascularity can be checked even though they are not the only factors.

For the fallopian tubes, laparoscopy is the only golden standard. The other method is Hysterosalpingogram or HSG. We send a radio opaque dye into the uterus and take an X-ray image. If the tubes are not blocked, the dye should spill into the abdomen. But vascular spilling where the dye spills into the blood vessels may also look like unblocked tubes. There’s a 25% chance for a false positive so it’s not a very popular practice.

Apart from these, hormone analysis has become very important because thyroid and prolactin conditions affect pregnancy. If the sperm count is low, hormone analysis is done because there are certain situations where a hormone imbalance might be the problem and can be resolved easily. For females, hormone analysis is always done because it’s part of the pregnancy.

Is infertility more prevalent in males or in females?

It’s not sure whether infertility is more prevalent in either males or females. It is believed that a hyper-fertile sperm or egg can compensate for a sub-fertile egg or sperm. The cause of infertility can be split as 40% male, 40% female and 20% unexplained reasons.

People are now willing to talk more about it.

How much does the lifestyle and environment weigh in on infertility?

Lifestyle and environment have a huge role in this. There are a lot of examples and there’s a theory that has been going around. It hasn’t been proved yet. Think about all the fertilisers we put in our plants. They’re all hormone disrupting factors. Similarly, the chicken you eat is pumped with oestrogen. Males with high oestrogen will obviously have a less than healthy reproductive system. In the case of females, you can’t have oestrogen all the time and expect to get pregnant. You can’t have an abundance of oestrogen of unknown types in the middle of the luteal phase and expect to get pregnant. Everything from our soaps and shampoos have endocrine disrupting factors.

Also, all our lives have become so sedentary. Most people sit and work for 8 – 10 hours. What kind of life is that? We’re so concentrated on our career that we are losing out on our health. We don’t even do one hour of exercise per day. We don’t even have the habit of walking. Since the introduction of automobiles, we don’t even bother about walking. And that’s the problem. Lifestyle diseases cause so much of the infertility now.

How do you council your patients about their infertility? Do you face any problems in getting them to accept it?

Personally, I keep everything transparent. I make them sit with me after every consultation, even if it’s a simple small follicular monitoring scan, I make sure that they sit with me and I explain to them what is happening. Sometimes, my patients know so much from listening that they are able to handle other patients if they are not confident about what’s going on. I think it helps to have a more colloquial way of explaining than what I do. Maybe because of this, I never had any issues with convincing my patients that they have a problem, maybe one in three hundred patients. Only if they accept that they have a problem can we start working on the solution.

Is it possible to produce gametes from stem cells and use them?

There has been study where they used a mouse’s stem cell to produce a sperm but that’s about it. The oocyte is simply too complex. We might be able to make sperm cells in maybe 5 years. We don’t even know the composition of an egg. An egg matured in vitro lacks most of the proteins present in an in vivo matured egg. So, egg cells seem a long way out. Males might be able to make sperm cells from their skin cells. But, that’s not allowed, is it? Instead of taking an adult, diploid cell and reducing it to a haploid to use it as a gamete, cloning would be much easier. It’s the same thing, just without the haploidization.

Since patients are willing to accept this much, how much help does the government provide?

I don’t think there is any governmental support for IVF, since we’re mostly concentrating on population control. But they are trying to bring in some guidelines which would make this treatment more ordered. But it’s too draconian to be implemented. I wouldn’t want to do third party reproduction at all after that. Because the moment they find some mistake in my work, they will fine my 10 or 15 lakhs and put me in jail immediately. So, in our country, after murderer and rapist, doctors can be put in jail without any questions. There aren’t many labs or colleges that have a lab with the basic necessities.

As a mother and an embryologist, how do you look at an embryo?

Every embryo is a baby for me. I would not throw away a healthy looking embryo even after eight years even if the parents want me to discard the embryo. I just don’t have the heart to discard any single good looking embryo which might be viable. I hope that someday my patients will get bored of my mails and tell me to donate them to someone else, because, you don’t throw away your baby in a dustbin. You give it away to some orphanage so that some other parent can adopt them.

In the context of technological advancements, do you think we have enough help from the government?

No. As much as I would like to say yes, the answer is no. Because the main policy of our country is population control, they don’t concentrate much on the issue. Setting up an IVF lab and maintaining it costs about a crore, which is a pittance because the government doesn’t do it. But there are several private companies that do bits and pieces of the work. That’s why I have a bunch of booklets on my table. I can just call up any company and tell them I’m sending samples and they can do it. But it costs more. If there was government aid, it would be nice.

Awareness is the most important and deficient resource that most life science issues have and it is our duty as fellow human beings to educate others.

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On our quest to answer questions about genetics that aren’t being asked as often as they should be, we found ourselves in the presence of an expert on the subject (in this case, Infertility). Dr. Priya Kannan, a prominent Embryologist and Consultant in Reproductive health and Human genetics. Though...Nishanth ThirugnanamNishanthThirugnanamtshark96@gmail.comAuthorGeneticEngg.com